The proposed studies will embrace 2 broad areas of steroid hormone research - metabolism and mechanisms of action. In the former category the following investigations are contemplated: 1) Study the metabolism of androstenedione and estriol in homogenates of human breast cancer tissue. The question asked is whether metabolic pathways could be correlated with the pathology or estrogen receptor content of the tumor. 2) An inquiry into the origin of the very high concentrations of estriol-3-sulfate in human breast cyst fluid. The patient will be given a tracer injection of 3H-estriol-3-sulfate at a prescribed interval prior to drainage of the cyst. Comparisons will be made of the endogenous and exogenous estriol-3-sulfateconcentrations between that in the cyst and the blood. 3) Profiles of estriol conjugates will be determined in abnormal pregnant states (e.g., toxemia, polycystic kidney disease) and comparisons will be made with normal pregnancy. The area of mechanism of action will center on the appearance of proteases and protease inhibitors in the immature mouse uterus shortly after estradiol stimulation. Of particular interest is the increase in elastase-like activity which we observed in the uterus, in vivo and in vitro, within 2 hours after estrogen administration. Several aspects of the nature of the protease activity will be studied. Human endometrium obtained at surgery will be analyzed for similar enzyme activities and the concentrations will be related to the endocrine state of the patient.